sulindac in preventing breast cancer in women at high risk for breast cancer

Conditions: Breast Cancer

Summary: rationale: chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. the use of sulindac may prevent breast cancer. purpose: this randomized phase i trial is studying the effects of sulindac, to prevent breast cancer, in women at high risk for breast cancer.

objectives: primary * determine the partitioning of sulindac and its metabolites in women at high risk for breast cancer by measuring drug and metabolite levels in nipple aspirate fluid (naf) after 6 weeks of therapy. secondary * determine prostaglandin levels in the naf of patients treated with this drug. * determine if nag-1 levels are induced in the naf of patients treated with this drug. * determine if c-reactive protein levels are reduced in the naf of patients treated with this drug. * determine if nag-1 levels and/or karyometric features in ductal epithelial cells are modulated in patients treated with this drug. outline: this is a randomized, open-label study. patients undergo nipple aspirate fluid (naf) collection. patients are then randomized to 1 of 2 treatment arms. * arm i: patients receive oral sulindac once daily. * arm ii: patients receive oral sulindac twice daily. in both arms, treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. all patients then undergo a second naf collection. after completion of study treatment, patients are followed at 2 weeks. projected accrual: a total of 30 patients (15 per treatment arm) will be accrued for this study.

Eligibility criteria:
disease characteristics: * meets 1 of the following criteria: * gail assessment score \> 1.7% risk for 5 years * history of lobular carcinoma in situ (pathology report required) * history of ductal carcinoma in situ (dcis) (pathology report required) * history of breast cancer in ≥ 1 first-degree relative or history of brca1 or brca2 positivity not treated with oophorectomy or mastectomy (test report required) * history of breast cancer in ≥ 2 second-degree relatives * any family history of breast cancer diagnosed prior to age 50 * personal history of breast cancer (invasive or dcis) with 1 breast intact * nipple aspirate fluid production ≥ 5 microliters * negative mammogram for breast cancer within the past 10 months * any suspicious breast masses must be examined by a clinical professional * hormone receptor status: * not specified patient characteristics: sex * female menopausal status * pre- or postmenopausal performance status * karnofsky 80-100% life expectancy * not specified hematopoietic * wbc ≥ 3,000/mm\^3 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * no history of bleeding or clotting disorder hepatic * bilirubin ≤ 2.0 mg/dl * ast and alt ≤ 2.0 times upper limit of normal * no indication of abnormal liver function renal * creatinine normal cardiovascular * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia gastrointestinal * no frequent, chronic, or moderate/severe gastric complaint * no upper gastrointestinal problems (e.g., symptoms of heartburn, dyspepsia, or abdominal pain) requiring prescription or nonprescription medical remedies more than once per week (on average) * no history of peptic ulcer or occult or gross intestinal bleeding other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no history of allergic reaction (e.g., urticaria, asthma, rhinitis) or gastric intolerance attributed to compounds of similar chemical or biological composition to sulindac * no history of allergy attributed to lidocaine, emla® cream, or xylocaine * no concurrent uncontrolled illness * no ongoing or active infection * no psychiatric illness or social situation that would preclude study compliance * no more than 2-3 servings of alcohol per week during study participation prior concurrent therapy: chemotherapy * more than 6 months since prior chemotherapy for breast cancer (invasive or dcis) endocrine therapy * more than 6 months since prior hormonal therapy for breast cancer (invasive or dcis) * no concurrent hormone-suppressing agents (e.g., tamoxifen or anastrozole) * no concurrent selective estrogen-receptor modulators * no concurrent aromatase inhibitors radiotherapy * more than 6 months since prior radiotherapy for breast cancer (invasive or dcis) surgery * see disease characteristics * no prior breast duct-disrupting surgery (e.g., mastectomy) that would preclude ductoscopy other * more than 3 months since prior warfarin or other systemic anticoagulant * more than 4-6 weeks since prior nonsteroidal anti-inflammatory drugs * no concurrent phenytoin or sulfonamides * no concurrent warfarin or other systemic anticoagulant * no other concurrent nonsteroidal anti-inflammatory drugs (including low-dose aspirin) * no concurrent large doses of supplements, vitamins (\> regular daily multivitamin) and/or herbal medicines (e.g., echinacea, ginkgo biloba, hypericum perforatum \[st. john's wort\], or herbal tea) * no other concurrent investigational agents

Keywords: breast cancer ductal breast carcinoma in situ lobular breast carcinoma in situ breast cancer in situ